Liver regeneration after extensive hepatectomy in rats: effect of preoperative chemotherapy with intravenous 5-fluorouracil

• Published in: Acta Cirúrgica Brasileira Vol. 37; no. 9; p. e370901
• Main Authors: Anghinoni, Marciano, Toderke, Edimar Leandro, Nakadomari, Thaísa Sami, Oliveira, Tiago Kuchnir Martins de, Locatelli, Felipe Pedrotti, Matias, Jorge Eduardo Fouto
• Format: Journal Article
• Language: English
• Published: Brazil Sociedade Brasileira para o Desenvolvimento da Pesquisa em Cirurgia 01-01-2022
• Subjects: 5-Fluorouracil; Animals; Fluorouracil - pharmacology; Hepatectomy; Ki-67 Antigen; Liver Regeneration; Proliferating Cell Nuclear Antigen; Rats; Rats, Wistar
• ISSN: 0102-8650; 1678-2674
• DOI: 10.1590/acb370901

To evaluate the effect of preoperative intravenous chemotherapy with 5-fluorouracil on liver regeneration in an experimental model of major hepatectomy in rats.
Wistar rats were divided into two groups of 20 animals each and submitted to 70% hepatectomy 24 h after intravenous injection of 5-fluorouracil 20 mg/kg (fluorouracil group, FG) or 0.9% saline (control group, CG). After hepatectomy, each group was subdivided into two subgroups of 10 animals each according to the day of sacrifice (24 h or 7 days). Liver weight during regeneration, liver regeneration rate using Kwon formula, and the immunohistochemical markers proliferating cell nuclear antigen (PCNA) and Ki-67 were used to assess liver regeneration.
At early phase (24 h after hepatectomy) it was demonstrated the negative effect of 5-fluorouracil on liver regeneration when assessed by Kwon formula (p < 0.0001), PCNA analysis (p = 0.02). With regeneration process complete (7 days), it was possible to demonstrate the sustained impairment of chemotherapy with 5-fluorouracil on hepatocytes regeneration phenomenon when measured by Kwon formula (p = 0.009), PCNA analysis (p = 0.0001) and Ki-67 analysis (0.001).
Preoperative chemotherapy with intravenous 5-fluorouracil negatively affected the mechanisms of liver regeneration after major hepatectomy in rats.